The proliferative states of density subpopulations of granulocyte-macrophage progenitor cells

Possible variation in proliferative state among subpopulations of myelopoietic progenitor cells of mouse bone marrow (CFU-c), which form in vitro colonies of granulocytes and/or macrophages, was investigated by estimation of the percentage in S phase of the cell cycle. Subpopulations of CFU-c, obtained by separation of femoral marrow cells on continuous albumin density gradients, were detected by culture in agar with different types of colony stimulating factor (CSF). The percentage of CFU-c in S phase, detected with mouse lung conditioned medium (CSFMLCM), averaged 17%. This was significantly lower than the 41% which was found when an extract of human urine (CSFHU) was used. This result was obtained with unfractionated marrow cells both by in vitro suicide with tritiated thymidine and by in vivo administration of hydroxyurea. There were different CFU-c responses to CSF, on the basis of their density distributions. Those responding to CSFMLCM had a low density disposition whereas the CSFHU responders had a high density disposition. The administration of hydroxyurea resulted in an alteration in the density distribution which indicated that a larger proportion of high density CFU-c were in S phase. The results indicate that CFU-c responding to different types of CSF differ in buoyant density and proliferative state.